ABergic asthma is characterized by airway inflammation and hyperreactivity upon exposure to allergens. Although the etiology of this disease is unknown, studies have shown an association of activated T lymphocytes in human asthma. Two distinct sets of CD4+ T cells have been described; Th2 cells produce Interleukin-4 (IL-4) and IL-5 whereas Th1 cells produce IL-2 and Interferon-gamma. IL-4 and IL-5 are important in the IgE response and eosinophilia, respectively. We have described a murine model in which inbred strains of mice develop many of the characteristics of allergic asthma following antigen-challenge, that is, airway hyperreactivity and eosinophilic inflammation; other murine strains do not develop such responses. We have shown that the allergic response of susceptible mice is CD4+ T cell-dependent and is associated with increases in IL-4 and IL-5. The overall hypothesis of this proposal is that the Th2 cytokine pattern is responsible for the airway inflammation anhyperreactivity following antigen exposure in susceptible mice. First, we will compare the lung cytokine profiles of susceptible and resistant mice after exposure to antigen and determine the cellular source of these cytokines. Second, we will examine the immunoregulatory roles of IL-4 and IL-12. These experiments should bring further insight into the immunologic basis of airway inflammation and hyperreactivity and should provide a unique opportunity to begin determining the pathogenesis of asthma.